NDUFA4

Last update 08 May 2025

Basic Info

Synonyms

CI-9k, CI-MLRQ, Complex I-MLRQ

+ [8]

Introduction

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (PubMed:22902835). NDUFA4 is required for complex IV maintenance (PubMed:22902835).

100 Clinical Results associated with NDUFA4

100 Translational Medicine associated with NDUFA4

0 Patents (Medical) associated with NDUFA4

107

Literatures (Medical) associated with NDUFA4

01 Dec 2025·Functional & Integrative Genomics

Identification and mechanistic analysis of shared biomarkers and pathogenesis in acute pancreatitis and sepsis based on differential gene expression and protein interaction networks

Article

Author: Lu, Weina ; Zheng, Cheng ; Chen, Qingqing ; Mao, Yifeng ; Cai, Shangwen ; Lan, Jian ; Xu, Panpan ; Xu, Chenghua

Acute pancreatitis (AP) is a common gastrointestinal inflammatory disease that requires hospitalization, with 40-70% of patients in moderate to severe stages potentially developing sepsis, which is closely related to high mortality rates and poor prognosis. Therefore, early identification of AP patients at risk of developing sepsis is crucial for reducing mortality. This study aims to identify core genes associated with sepsis to provide new core genes for early warning and management of patients with acute pancreatitis. The study utilized the GSE54514, GSE57065, GSE95233, and GSE194331 datasets for analysis, employing weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network construction. Six core genes were identified using two machine learning methods and validated with the GSE3644 and GSE28750 datasets. The analysis revealed that the identified core genes (NDUFA1, COX7A2, COX7B, UQCRQ, SNRPG, and NDUFA4) are related to the oxidative phosphorylation (OxPhos) pathway, and significant differences were observed in the immune cell composition between AP and sepsis patients. SNRPG may play a role in the progression from AP to sepsis by regulating NDUFA4, linking it to cellular metabolism and redox balance. The newly identified core genes and their associated molecular mechanisms provide important clinical insights into the progression of acute pancreatitis to sepsis, potentially offering new research directions for future therapeutic strategies. Clinical trial number: This study was approved by the Ethics Committee of (Municipal Hospital affiliated to Taizhou University), in accordance with the Declaration of Helsinki. Approval number: LWSL202400220.

01 Apr 2025·Human Genetics and Genomics Advances

Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease

Article

Author: Deniz, Engin ; Friedland-Little, Joshua ; Lam, Christina T ; Beckman, Erika ; Shelkowitz, Emily ; Viviano, Stephen ; Marquez, Jonathan ; Thies, Jenny

Most of the chemical energy that organisms rely on to support cellular function is generated through oxidative phosphorylation, a metabolic pathway in which electron donors NADH and FADH are oxidized through a series of successive steps to generate adenosine triphosphate. These redox reactions are orchestrated by a series of five protein complexes that sit within the mitochondrial membrane. Deficiency of cytochrome c oxidase, the fourth of these complexes, is a recognized cause of mitochondrial disease. COXFA4 encodes one of the protein subunits of cytochrome c oxidase, and variants in COXFA4 have recently been reported in individuals with a range of symptoms. These symptoms can include feeding difficulties, poor growth, cardiomyopathy, Leigh or Leigh-like disease, and neurodevelopmental delay, although these symptoms vary widely between individuals. However, a mechanistic understanding of the connection between COXFA4 loss and these varied disease manifestations is lacking. Using animal modeling in Xenopus, we explored the ramifications of coxfa4 loss of function on the early developing heart. We then conducted a hypothesis naive analysis of cellular gene expression in the context of COXFA4 deletion and discovered a downstream deficiency in the ornithine decarboxylase pathway. Small-molecule-based modulation of the ornithine decarboxylase pathway in our model modified the extent of disease, including improvement of cardiac function. Our findings point to a mechanism by which COXFA4 dysfunction leads to tissue-specific disease.

04 Mar 2025·British Poultry Science

Consensus gene co-expression analysis across multiple intestinal tissues to identify key genes and pathways associated with abdominal fat deposition in broilers

Article

Author: Wang, S. ; Zhang, R. ; Lu, J. ; Qin, Z. ; Yuan, H. ; Liu, S. ; Liu, Y.

1. Abdominal fat deposition (AFD) is regulated by multiple intestinal tissues, and changes in the function of intestinal tissues are associated with AFD. Currently, integration of transcriptomic data across multiple intestinal tissues to explore excessive AFD has rarely been reported in broilers.2. In this study, a consensus gene co-expression network across the duodenum, jejunum, ileum and caecum of high- and low-abdominal fat broiler lines (HL and LL) was constructed using a publicly available transcriptomic data set. Combining the results of functional enrichment analyses and differential gene expression analyses, this investigated the genes and biological pathways across the four intestinal tissues that might influence AFD.3. In one expression module, NDUFA5, NDUFS6, NDUFA4, NDUFS4, ATP5H, ATP5J and ATP5C1 were significantly enriched in the oxidative phosphorylation pathway, with GPX2 and GSR significantly enriched in the glutathione metabolism pathway. These genes were significantly downregulated in the four intestinal tissues of the HL compared to LL chickens, which may be associated with AFD by increasing intestinal permeability.4. Lipid metabolism relevant genes were identified in other modules (ALDH7A1, ACSBG1, THEM4 and DECR1), which may be linked to AFD through regulation of lipid metabolism. Interestingly, in the first module, 12 genes were significantly enriched in the proteasome pathway and significantly downregulated in the four intestinal tissues in HL birds compared to LL birds, indicating a link between the proteasome and AFD.

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NDUFA4

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